Background: Citrin, encoded by SLC25A13, is a component of the malate-aspartate shuttle, which is the main NADH-transporting system in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), which usually resolves within the first year of life. However, small numbers of adults with citrin deficiency develop hyperammonemic encephalopathy, adult-onset type II citrullinemia (CTLN2), which leads to death due to cerebral edema. Liver transplantation is the only definitive therapy for patients with CTLN2. We previously reported that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. Citrin deficiency may impair the glycolysis in hepatocytes because of an increase in the cytosolic NADH/NAD+ ratio, leading to an energy shortage. MCT administration can provide energy to hepatocytes and was expected to have a good effect on CTLN2.

Methods: An MCT supplementation therapy under a low-carbohydrate formula was administered to five patients with CTLN2. Four of the patients had episodes of hyperammonemic encephalopathy, and one patient had postprandial hyperammonemia with no symptoms.

Results: One of the patients displaying hyperammonemic encephalopathy completely recovered with all normal laboratory findings. Others notably improved in terms of clinical and or laboratory findings with no hyperammonemic symptoms; however, the patients displayed persistent mild citrullinemia and occasionally had postprandial mild hyperammonemia most likely due to an irreversible change in the liver.

Conclusions: An MCT supplement can provide energy to hepatocytes and promote hepatic lipogenesis, leading to a reduction in the cytosolic NADH/NAD+ ratio. MCT supplementation under a low-carbohydrate formula could be a promising therapy for CTLN2 and should also be used to prevent CTLN2 to avoid irreversible liver damage.

f0040: Changes in the levels of plasma citrulline and Fischer ratio in Case 3.The open and closed squares indicate the changes in the levels of plasma citrulline and the Fischer ratio, respectively.The patient did not take Macton oil regularly from days 90–280 of therapy.

Mentions:
The patient was treated with a supplement of 30 mL of Macton oil under a low-carbohydrate formula. The fatigability and watery diarrhea disappeared within a month of therapy. He initially improved in the levels of postprandial blood ammonia, plasma glutamine and Fischer ratio. As shown in Fig. 1, Supplementary Fig. 5, he did not display any further improvement from 90 to 280 days of therapy because of an insufficient intake of Macton oil. He then took it regularly and displayed an improved Fischer ratio. After 11 months of treatment, his body weight increased to 50 kg. He had no apparent symptoms, but he had persistent mild citrullinemia.

f0040: Changes in the levels of plasma citrulline and Fischer ratio in Case 3.The open and closed squares indicate the changes in the levels of plasma citrulline and the Fischer ratio, respectively.The patient did not take Macton oil regularly from days 90–280 of therapy.

Mentions:
The patient was treated with a supplement of 30 mL of Macton oil under a low-carbohydrate formula. The fatigability and watery diarrhea disappeared within a month of therapy. He initially improved in the levels of postprandial blood ammonia, plasma glutamine and Fischer ratio. As shown in Fig. 1, Supplementary Fig. 5, he did not display any further improvement from 90 to 280 days of therapy because of an insufficient intake of Macton oil. He then took it regularly and displayed an improved Fischer ratio. After 11 months of treatment, his body weight increased to 50 kg. He had no apparent symptoms, but he had persistent mild citrullinemia.

Background: Citrin, encoded by SLC25A13, is a component of the malate-aspartate shuttle, which is the main NADH-transporting system in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), which usually resolves within the first year of life. However, small numbers of adults with citrin deficiency develop hyperammonemic encephalopathy, adult-onset type II citrullinemia (CTLN2), which leads to death due to cerebral edema. Liver transplantation is the only definitive therapy for patients with CTLN2. We previously reported that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. Citrin deficiency may impair the glycolysis in hepatocytes because of an increase in the cytosolic NADH/NAD+ ratio, leading to an energy shortage. MCT administration can provide energy to hepatocytes and was expected to have a good effect on CTLN2.

Methods: An MCT supplementation therapy under a low-carbohydrate formula was administered to five patients with CTLN2. Four of the patients had episodes of hyperammonemic encephalopathy, and one patient had postprandial hyperammonemia with no symptoms.

Results: One of the patients displaying hyperammonemic encephalopathy completely recovered with all normal laboratory findings. Others notably improved in terms of clinical and or laboratory findings with no hyperammonemic symptoms; however, the patients displayed persistent mild citrullinemia and occasionally had postprandial mild hyperammonemia most likely due to an irreversible change in the liver.

Conclusions: An MCT supplement can provide energy to hepatocytes and promote hepatic lipogenesis, leading to a reduction in the cytosolic NADH/NAD+ ratio. MCT supplementation under a low-carbohydrate formula could be a promising therapy for CTLN2 and should also be used to prevent CTLN2 to avoid irreversible liver damage.